Association Between Maternal C-Reactive Protein (CRP) Levels and Adverse Neonatal Outcomes: A Systematic Review and Meta-Analysis

Background: C-reactive protein (CRP), a biomarker of systemic inflammation, has been implicated in adverse pregnancy and neonatal outcomes. However, the relationship between maternal CRP and neonatal complications remains unclear. We conducted a systematic review and meta-analysis to synthesize available evidence. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library up to July 2025 for observational studies reporting maternal CRP levels in relation to neonatal outcomes. Eligible outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and stillbirth. Random-effects models were used to calculate pooled standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I2 statistic. Results: The search yielded 6843 records, of which 42 studies (comprising 18,393 pregnant women) met the inclusion criteria. Maternal mean CRP levels were significantly higher in adverse pregnancy outcomes compared with controls (SMD = 0.39; 95% CI 0.08–0.70; p = 0.01; I2 = 96.6%). Elevated CRP was strongly associated with PTB (OR = 3.81; 95% CI 2.66–5.47; p < 0.001; I2 = 85%; n = 23) and LBW (OR = 2.34; 95% CI 1.35–4.03; p = 0.002; I2 = 84.2%; n = 7). No significant associations were observed for SGA (OR = 1.14; 95% CI 0.86–1.49; p = 0.36; I2 = 0%; n = 5) or stillbirth (OR = 1.89; 95% CI 0.92–3.90; p = 0.08; I2 = 44.9%; n = 4). Conclusion: Maternal CRP is significantly associated with increased risks of preterm birth and low birth weight but not with SGA or stillbirth. These findings support the role of systemic inflammation in adverse neonatal outcomes and highlight the need for prospective studies to clarify causal mechanisms and assess the clinical utility of CRP in pregnancy risk stratification.